Kidney Transplant Rejection
Conditions
Brief summary
The ATDC-PICI study is a Phase Ib, single-arm, prospective, non-randomized, multicentric trial, to evaluate the safety of ATDC cell product as adjunctive therapy to standard of care (SOC) in highly sensitized kidney transplant recipients.
Detailed description
The study population is sensitized kidney transplant candidates (cPRA ≥ 90%) between 18 and 65 years. An algorithm has been designed to rank highly sensitized patients on the waiting list for kidney transplantation according to their likelihood of obtaining a suitable donor within the upcoming 12 months. The algorithm was designed based on an analysis of an immunologically matched historical cohort using data from the OCATT registry. Patients will be selected in accordance with the algorithm and proposed for inclusion in the study in a sequential manner until the required number of patients has been reached (n=30). Given the unpredictability and reduced likelihood of obtaining a compatible deceased kidney donor within an acceptable time frame for this study, the total number of patients to be included will be 2x superior to those who will receive treatment with ATDC (n=15). * 30 highly sensitized patients will be pre-included in the study. * The first 15 highly sensitized patients that obtain a compatible deceased kidney donor will be included in the study.
Interventions
BIOLOGICALAutologous Tolerogenic Dendritic Cells
• Autologous Tolerogenic Dendritic Cells (D+1 to D+3 post-transplantation), ATDC, 1 million ATDC/Kg over a period of 30 minutes (up to 1 hour) will administer between Day 1 and Day 3 after transplantation.
Sponsors
Fundacion Clinic per a la Recerca Biomédica
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Highly sensitized (cPRA ≥ 90%) kidney transplant candidates between 18 and 65 years old. 2. To be selected by the algorithm according to probability of kidney transplantation in the upcoming 12months. 3. Adequate venous access and absence of contraindications for leukoapheresis. 4. Women of childbearing age must take contraceptive measures. 5. Must have given written informed consent
Exclusion criteria
1. Subjects with active TB. 2. Patients on the waiting list multiple organ transplants. 3. A significantly abnormal general serum screening lab result defined as WBC\<3.0x103/ml, Hgb\<8.0 g/dL, platelet count \<100x103/ml, SGOT\>3x upper limit. 4. HIV-positive subjects. 5. Subjects who test positive for HBV infection \[positive HBVsAg or HBVeAg/DNA\] or HCV infection \[RNA+\]. 6. Subjects with active CMV or EBV infection as defined by positive PCR. 7. Subjects with a known history of previous myocardial infarction within one year of screening. 8. Subjects with a history of clinically significant thrombotic episodes, and subjects with active peripheral vascular disease. 9. Patients with a kidney disease with high risk of recurrence and/or complement-associated kidney disease (aHUS, etc). 10. Pregnant and lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Side effects of ATDC cell product in highly sensitized patients who received a kidney from a deceased donor. | at day 1 and day 3 | Proportion of patients with toxicity/side effects during and after administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate incidence of biopsy proven acute rejection episodes in patients treated with ATDC as adjunctive therapy to SOC | at 3 and 12months after transplantation. | Incidence of BPAR at 3 and 12months after transplantation. |
| To evaluate renal function up to 1 year after transplantation | at 3, 6 and 12 months after transplantation | Renal function at 3, 6 and 12 months after transplantation as assessed by estimated glomerular filtration rate (eGFR) |
| Rate of infectious disease that required hospitalization at 6 and 12 months. | at 6 months and 12 months. | Proportion of patients with severe or serious infections at 6 months and 12 months. |
| To evaluate graft survival | at 12 months after transplantation | Graft survival at 12 months after transplantation |
| To characterize the immunophenotype status. | 24 months | Define the different cell subtypes in circulating cells, as well as the functionality of T and B cells using ELISpot and Fluorospot techniques |
| To evaluate patient survival | at 12 months after transplantation | Patient survival at 12 months after transplantation |
Countries
Spain
Contacts
Primary ContactFritz Diekmann, Dr
Backup ContactMaria Joyera
Outcome results
None listed